Mohammed T. Abou-Saleh

SINGLE-PHOTON EMISSION COMPUTERIZED TOMOGRAPHY 365widely used in static SPECT studies of dementia. These havegenerally reported that patients with AD have deficits in flow whichare maximal bilaterally in the parietotemporal cortex, whilepatients with MID vary from having a normal pattern to markedasymmetrical focal deficits anywhere in the cortex. Sharp et al. 8found that, despite having characteristic regional abnormalities onSPECT, the majority of patients with AD had a normal appearancein those regions on magnetic resonance imaging (MRI). Ebmeier etal. 9 found that while MRI was not able to differentiate between ADand MID, 19 out of 21 patients showed bilateral deficits on IMPSPECT scans. Although the distribution of 123 I-IMP initiallyreflects the rCBF, redistribution of the tracer occurs approximately1 h after injection. The use of 123 I-IMP is also limited by therestricted availability of 123 I, which has a half-life of 13 h, and iscostly to produce, as this requires a cyclotron.99mTc-HMPAO SPECT99m Technetium is readily available from commercial generators innuclear medicine departments, is inexpensive and has a shorterhalf-life (6 h) and better dosimetry than 123 I. Labelling with 99m Tcis a much more complex procedure than with 123 I and thedevelopment of a 99m Tc-labelled compound to provide a measureof rCBF was a major advance in SPECT technology. Technetiumlabelledhexamethyl propylenaemine oxime (HMPAO) is alipophilic tracer which, after intravenous administration, crossesthe blood–brain barrier with high extraction and is retained in thebrain in hydrophilic form. The brain uptake occurs over the first2 min and has a stable distribution for many hours. This enablesconventional equipment to be used to detect the radiation emittedfrom the brain. Comparative studies with PET in humans reveal atendency to underestimate flow in areas of high rCBF but a goodcorrelation with areas of low and medium rCBF. Although 99m Tc-HMPAO cannot, at present, be used to quantify rCBF absolutely,the results can be expressed semi-quantitatively by comparing thecounts in each brain region of interest (ROI) to a reference area,such as the whole brain or cerebellum.A number of SPECT studies have now been performed using99m Tc-HMPAO to investigate dementia and the characteristics ofthese are shown in Table 67.1. The studies varied in thepopulations studied, diagnostic criteria used and the methods ofassessment of images. Some of these studies had no data oncontrol subjects for comparison. The majority carried out initialscreening with CT or MRI to exclude structural lesions.The early studies used qualitative assessment of the images andfound that most patients with AD had bilateral parietotemporaldeficits; those who did not tended to be less impaired cognitively 10 .Frontal deficits were also seen in AD. Deficits were lesscommon in MID than AD, particularly when known infarcts onMRI were excluded, and they occurred in a more variable andasymmetrical pattern. Neary et al. 11 also investigated patients withprogressive supranuclear palsy (PSP) and others with the clinicalsyndrome of dementia of frontal-lobe type, which is consistentwith, although not necessarily diagnostic of, Pick’s disease.The later studies have generally been semi-quantitative. When arotating g-camera has been used, the whole brain is scanned andthe cerebellum has usually been chosen as the reference area, as itis relatively unaffected by the pathology of AD 12 . Also, patientswith AD have a normal cerebellar metabolic rate of glucose,compared with elderly controls, on PET study 13 . A recent studyvalidated the use of the cerebellum as a reference region forSPECT quantification in patients with AD 14 . Studies usingdedicated head scanners, which acquire their data in the form oftransverse tomographic slices, have not usually obtained cerebellardata, so they have used the occipital region as a reference areabecause the latter also appears relatively unaffected by AD 15 .These studies have consistently found that patients with AD havea bilateral decrease in rCBF in the posterior temporal and parietalregions, adjacent to the occipital lobe, and sometimes the frontallobes are affected, although the basal ganglia are not (Table 67.1).Several studies have demonstrated correlations in AD betweenrCBF and neuropsychological function, and these have tended tobe more apparent for language, praxis and global function thanfor memory 15,19 . Recent studies of AD have also evaluated thecorrelates of changes in CBF in relation to psychopathology andbehaviour disturbance. Reduced frontal CBF in AD is associatedwith negative symptoms 20 , with presence of delusions 24 , disinhibitedbehaviour, apathy and blunted affect 22 .Pharmacological activation studies of the effect of centralcholinergic stimulation upon rCBF in AD have recently beenreported. These require paired SPECT studies, basal (after salineinfusion) and activated (after infusion of a cholinergic agent, e.g.physostigmine). In patients with AD, the reduced rCBF in theposterior parietotemporal region in the basal scan was focallyincreased in the scan after the cholinergic agent, which did notoccur in control subjects 19 . AD is associated with strikingabnormalities in the central cholinergic system, of a functionalcholinergic deficit that is at least partly reversible. Also a SPECTstudy of nootropic drugs showed regional improvement in CBF 23 .Donepezil treatment in AD was associated with a significantincrease in CBF in the frontal lobes 24 .Studies have also addressed the diagnostic value of SPECT indifferentiating AD from other types of dementia. Dementia withLewy bodies (DLB) is associated with reduced frontal CBF thanAD 25 . Importantly DLB is associated with severe degeneration ofthe dopamine system as shown by a recent SPECT study 26 .Primary progressive aphasia is associated with reduced CBF infronto-temporal regions 27 . Fronto-temporal dementia FTD ischaracteristically associated with reduced CBF in frontotemporalregions 28 . Alzheimer’s disease and FTD could bedifferentiated by discriminant analysis applied to 99m Tc-HMPAO SPECT data with 100% correct classification of patientswith FTD and 90% correct clarification of patients with AD 29 .Moreover fronto-temporal dementia is characterized by earlynon-cognitive behavioural changes with relatively spared cognitivefunction, frontal atrophy and SPECT deficits in CBF infrontal and temporal regions whilst AD is associated with earlycognitive changes and medial temporal and parietal-temporaldeficits in CBF 38 .Patients with Korsakoff’s psychosis, in contrast to patients withAD, have normal rCBF in the posterior temporal region.It is well established that Parkinson’s disease (PD) ischaracterized by degeneration of dopaminergic neurons in thesubstantia nigra, which project to the corpus striatum. In anHMPAO SPECT study, 36 patients with PD were found, overall,to have normal rCBF in the caudate and putamen; however, thoseon no therapy had lower rCBF, and those on L-dopa-replacementtherapy had higher rCBF, in the caudate and putamen, thancontrols. Bilateral reductions in rCBF in the parietal region,similar to those found in AD, were also found in patients withPD. No patients had focal lesions on CT scans. Interestingly, theparietal reductions in rCBF were more pronounced in those PDpatients with cognitive impairment and those receiving chronicanticholinergic therapy. Dopamine deficiency is the main, but notthe only, neurochemical deficit in PD, and these SPECT findingsare consistent with the concept that AD and PD may overlap tosome extent. Patients with Huntington’s Disease (HD), characterizedby chorea and progressive dementia, have reduced rCBF inthe caudate nucleus, matched by caudate atrophy on MRI.However, the size of the rCBF deficit in the SPECT studyexceeded that predicted by the MRI findings 39 .There has been a case report of a patient with pathologicallyproven Creutzfeldt–Jakob disease, who had strikingly reduced